Dose Escalation Study of Cyclophosphamide in HIV-Infected Subjects on HAART Receiving SB-728-T

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Sangamo Biosciences
Sponsor:
Information provided by (Responsible Party):
Sangamo Biosciences
ClinicalTrials.gov Identifier:
NCT01543152
First received: March 1, 2012
Last updated: February 19, 2014
Last verified: February 2014

March 1, 2012
February 19, 2014
December 2011
September 2014   (final data collection date for primary outcome measure)
Treatment related Adverse Events on subjects who received cyclophosphamide prior to SB-728-T infusion [ Time Frame: 28 days after the SB-728-T infusion of the last subject in each Cohort and up to 12 months ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01543152 on ClinicalTrials.gov Archive Site
  • Effect of escalating doses of cyclophosphamide on SB-728-T engraftment as measured by pentamer PCR [ Time Frame: Up to 12 months after the last SB-728-T infusion ] [ Designated as safety issue: No ]
  • Effect of SB-728-T on plasma HIV-1 RNA levels following HAART interruption [ Time Frame: Up to 12 months after the last SB-728-T infusion ] [ Designated as safety issue: No ]
  • Change in CD4+ T-cell counts in peripheral blood after treatment with SB-728-T [ Time Frame: Up to 12 months after the last SB-728-T infusion ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Dose Escalation Study of Cyclophosphamide in HIV-Infected Subjects on HAART Receiving SB-728-T
A Phase I, Open-Label Study to Assess the Effect of Escalating Doses of Cyclophosphamide on the Engraftment of SB-728-T in Aviremic HIV-Infected Subjects on HAART

The purpose of the study is to evaluate the safety, tolerability and effect on HIV viral load, of escalating doses of cyclophosphamide administered 1 day prior to SB-728-T infusion.

The objectives of the study are to augment HIV-specific T-cells and to reverse or decrease the progressive destruction of CD4+ T-cells that leads to clinical AIDS. Levels of engraftment vary from negligible to about 10% of the CD4+ T-cells in the vascular compartment. Preliminary analyses of HAART TI suggest that an anti-HIV effect may correlate with the level of SB-728-T engraftment. Concurrently, non-myeloablative lymphodepletion with cyclophosphamide has been demonstrated to enhance engraftment of adoptively transferred T-cells through a variety of mechanisms. The study is being undertaken to increase SB-728-T engraftment through the administration of low non-myeloablative doses of cyclophosphamide.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV
  • Genetic: SB-728-T
    Infusion will be 5 to 30 billion ZFN modified CD4+ T cells 1 day following IV cyclophosphamide 200 mg
    Other Name: cyclophosphamide
  • Genetic: SB-728-T
    Infusion will be 5 to 30 billion ZFN modified CD4+ T cells 1 day following IV cyclophosphamide 0.5 g/m2
    Other Name: cyclophosphamide
  • Genetic: SB-728-T
    Infusion will be 5 to 30 billion ZFN modified CD4+ T cells 1 day following IV cyclophosphamide 1.0 g/m2
    Other Name: cyclophosphamide
  • Experimental: Cohort 1 - IV cyclophosphamide 200 mg
    Intervention: Genetic: SB-728-T
  • Experimental: Cohort 2 - IV cyclophosphamide 0.5 g/m2
    Intervention: Genetic: SB-728-T
  • Experimental: Cohort 3 - IV cyclophosphamide 1.0 g/m2
    Intervention: Genetic: SB-728-T
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
18
September 2015
September 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male or female, 18 years of age or older with documented HIV diagnosis within 10 years of screening.
  • Must be willing to comply with study-mandated evaluations; including discontinuation of current antiretroviral therapy during the treatment interruption.
  • Must have received at least 6 months of continuous HAART therapy and have had undetectable VLs for the preceding 3 months.
  • On stable antiretroviral medication (no changes to treatment within 4 weeks of screening.
  • CD4+ T-cell count ≥500 cells/µL.
  • Undetectable HIV-1 RNA obtained at screening.
  • ANC ≥2500/µL
  • Platelet count ≥200,000/µL

Exclusion Criteria:

  • Acute or chronic hepatitis B or hepatitis C infection.
  • Active or recent (in prior 6 months) AIDS defining complication.
  • Any cancer or malignancy within the past 5 years, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin or low grade (0 or 1) anal or cervical dysplasia.
  • Current diagnosis of NYHA grade 3 or 4 CHF, uncontrolled angina or arrhythmias.
  • History or any features on physical examination indicative of a bleeding diathesis.
  • Received HIV experimental vaccine within 6 months prior to screening, or any previous gene therapy using an integrating vector.
  • Use of chronic corticosteroids, hydroxyurea, or immunomodulating agents within 30 days prior to screening.
  • Use of Aspirin, dipyridamole, warfarin or any other medication that is likely to affect platelet function or other aspects of blood coagulation during the 2 week period prior to leukapheresis.
  • Currently participating in another clinical trial or participation in such a trial within 30 days prior to screening visit.
  • Subjects who are currently taking maraviroc or have received maraviroc within 6 months prior to screening.
Both
18 Years and older
No
Contact: Donna Bednarski dbednarski@sangamo.com
United States,   Puerto Rico
 
NCT01543152
SB-728-1101
Yes
Sangamo Biosciences
Sangamo Biosciences
Not Provided
Study Director: Winson Tang, M.D. Sangamo BioSciences, Inc.
Sangamo Biosciences
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP